Synthesis of 1-hydroxy-4-keto-alpha-ionone

ABSTRACT

Air oxidation of 4-keto- Alpha -ionone on solid surfaces to produce 4-(1-hydroxy-4-oxo-2,6,6-trimethyl-2-cyclohexene-1-yl)-3butene-2-one.

United States Patent Inventor Ralph Lawrence Rowland Winston-Salem, N.C.

Appl. No. 727,691

Filed May 8, 1968 Patented Sept. 21, 1971 Assignee R. J. Reynolds Tobacco Company Winston-Salem, N.C.

SYNTHESIS OF l-HYDROXY-4-KETO-a-IONONE 3 Claims, No Drawings US. Cl 260/587, 260/514 R, 260/586 R Int. Cl C07c 49/60 Field of Search 260/586, 587

Mousseron-Canet, C. R. Acad. Sc. Paris, 262 pp. 1397-1400 se'rie C, 1966) Primary Examiner Bernard Helfin Assistant Examiner-Norman P. Morgenstem Attorney- Pendelton, Neuman, Williams & Anderson ABSTRACT: Air oxidation of 4-keto-a-ionone on solid surfaces to produce 4-( l-hydroxy-4-oxo-2,6,6-trimethyl-2- cyclohexene-l-yl)-3-butene-2-one.

SYNTHESIS OF l-HYDROXY-4-KETO-a-IONONE This invention relates to a method of synthesizing 4-(1- hydroxy-4-oxo-2,6,6-trimethyl-Z-cyclohexene-lyl)-3-butene- 2-one.

in the copending application of Ralph Lawrence Rowland and Donald L. Roberts, Ser. No. 533,839, filed Mar. 14, 1966, now [1.8. Pat. No. 3,410,908, there is disclosed the novel compound 4-( l-hydroxy-4-oxo-2,6,6-trimethyl-2-cyclohexenel yl)-3-butene-2-one (which compound can also be designated l-hydroxy-4-keto-a-ionone). This compound finds particular utility in the preparation of the plant hormone abscisic acid, which chemically is 3-methyl-5-(l-hydroxy-4-oxo-2,6,6- trimethyl-2-cyclohexenel -y] )-cis, trans-2,4-pentadienoic acid. The use of lhydroxy-4-keto-a-ionone in the preparation of abscisic acid is disclosed in the said copending application and the disclosure therein is incorporated by reference herein.

it has now been found that 4-keto-a-ionone can be oxidized by air when the compound is contacted with selected solid surfaces, especially solid surfaces which are basic in character. Air oxidation of 4-keto-a-ionone in this manner produced 1- hydroxy-4-keto-a-ionone. The synthesis is particularly advantageous and convenient to conduct. Thus, the 4-keto-aionone dissolved in a suitable solvent such as, for example, hexane, pentane, benzene, ether, chloroform and the like is adsorbed on the surface of a solid adsorbent and air passed through the system to accomplish the desired conversion. The

period required for the conversion varies depending upon the activity of the solid adsorbent employed, but in general air oxidation is carried out for a period ranging from about 5 to 30 hours. The air oxidation can be conducted at ambient temperatures and the oxidized product eluted from the surface of the solid adsorbent using eluants such as ether, chloroform, methyl alcohol, ethyl alcohol, and mixtures thereof.

The air oxidation can be accomplished by bubbling air through a mixture consisting of 4-keto-a-ionone, a solid adsorbent, and a suitable organic liquid.

The solid adsorbent employed for the synthesis of the invention is one which is basic in character. A solid which is basic in character is a solid which, by its intrinsic character or by pos session of surface sites or by adsorption of surface groups acts as an electron donor in reaction with acids (i.e., Lewis Base) or a solid which, in the presence of water, functions in the production of hydroxide ions. Not all solid adsorbents promote the air oxidation of 4-keto-a-ionone to l-hydroxy-4- keto-a-ionone. Representative of the basic adsorbents which do promote the desired oxidation are alumina (aluminum oxide), magnesia (magnesium oxide), zinc oxide, calcium oxide, titanium dioxide, activated carbon and the like.

The synthesis of the present invention is further illustrated by the following specific examples.

EXAMPLE 1 A solution of 1.034 grams of 4-keto-a-ionone in milliliters of ether was added to a column of alumina mm. diam. x 210 mm. height). Several 5-milliliter portions of other were used to rinse the sample downward onto the adsorbent. After using a slight vacuum to pull dry air through the column for 18 hours, the organic material was eluted from the alumina with 200 milliliters of4:l chloroform-methyl alcohol. Concentration of the eluate gave a residue of 0.655 gram. The residue was identified as a mixture of l-hydroxy-4-keto-a-ionone (29 percent by weight), 4-keto-a-ionone (35 percent by weight), 7-hydroxy-4,4,7-trimethyl-4,6,7,8-tetrahydro-2(3H)- naphthalenone (25 percent by weight) and 4,4,7-trimethyl- 3,4-dihydro-2( lH)-naphthalenone (4 percent by weight).

EXAMPLE 2 Xwas deactivated in the following manner. Alumina (356 g.) was spread onto a tray (l4 l8") and was allowed to stand for one hour with occasional respreading. The alumina was then placed in a stoppered flask with 12 milliliters of water, was shaken thoroughly, and was allowed to stand at least 16 hours before use.

EXAMPLES 3-10 Varied solids were used as adsorbents for air oxidation of 4- keto-a-ionone by the procedure of Example 1, with the exception that (l) the 4-keto-a-ionone was added to zinc oxide in a chloroform solution and (2) elution of the reaction mixture from magnesium oxide, barium oxide and bismuth trioxide was accomplished using chloroform while elution from ferric oxide was accomplished using 4:1 ether-methyl alcohol. The

results are tabulated as follows:

Percent con- Time of Recovery version to air flow, of 4 keto- Lhydroxyi- Adsorbent hours a-ionone keto-a-ionone' Zinc oxide 22 Titanium dioxide 22 84 Calcium oxide. 22 84 Magnesium oxide 17 39 Activated carbon 22 81 Barium oxide 23 91 Bismuth trioxide 23 95 Ferric oxide 24 73 EXAMPLE 1 l A dilute hexane solution of 4-keto-a-ionone was added to a column of deactivated alumina and the column was rinsed with hexane. Flow of air through the alumina column which had adsorbed the 4-keto-a-ionone resulted in oxidation to yield l-hydroxy-4-keto-a-ionone.

EXAMPLE 12 A solution of 2.1 grams of 4-keto-a-ionone in 900 milliliters of hexane was stirred for 1 hour with 76 grams of deactivated alumina. The alumina was separated by filtration and air was allowed to flow through the filter bed for 20 hours. Washing of the alumina with a 4:1 chloroform-methyl alcohol mixture followed by concentration of the washings at reduced pressure yielded a residue of 1.7 grams. Vapor-phase chromatographic analysis showed that the residue contained more than 85 percent l-hydroxy-4-keto-achromatographic analysis showed that the residue contained more EXAMPLE 13 A solution of 0.273 gram of 4-keto-a-ionone in 50 milliliters of benzene was stirred at room temperature while air was bubbled through the solution for 48 hours. Unreacted 4-keto-aionone was recovered quantitatively by concentration under reduced pressure. 1

A mixture of 120 milliliters of benzene, 0.9 gram of 4-ketoa-ionone and 20 grams of alumina was stirred at room temperature for 4.5 hours with air bubbled through the mixture. The alumina was separated by filtration and was washed with milliliters of 9:1 ether-methyl alcohol. Concentration of the combined filtrate and washings yielded 0.65 gram of 4- keto-a-ionone and 0.1 1 gram of l-hydroxy-4-ketoa-ionone.

EXAMPLE l4 Oxidation was accomplished over a temperature range using the procedure of Example 2 with alumina as the adsorbent: at 6 C., l-hydroxy-4-keto-a-ionone was obtained in 26 percent conversion with 66 percent recovery of 4-keto-aionone after 2l.5 hours of air flow; at 50-62 C., with an air flow of 4 hours, l-hydroxy-4-keto-a-ionone was obtained in 32 percent conversion with percent recovery of 4-keto-aionone; at 90 C., with air flow for 2 hours, l-hydroxy-4-ketoa-ionone was obtained in 3 percent yield and a mixture of 7023023 chloroform-methyl alcohol-water was used to elute the product.

Those modifications and equivalents which fall within the spirit of the invention and the scope of the appended claims are to be considered part of the invention.

1 claim:

1. A process for preparing 4-( l-hydroxy-4-oxo-2,6,6- trimethyl-Z-cyclohexene-l-yl)-3-butene-2-one which comprises adsorbing 4-keto-a-ionone on the surface of a basic solid adsorbent and passing air over said surface containing ionone, a basic solid adsorbent and an organic solvent for 4-, I keto-a-ionone, said basic solid adsorbent being selected from the group consisting of metal oxides and activated carbon.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,607,942 Dated Sgptember' 21, L221 Inve to Ralph Lawrence Rowland It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, line 70, "x" should be Alumina Column 2, line 54, after "0:" insert -ionone. and

delete the remainder of the line.

Column 2, line 55, delete the entire line.

Column 4, line 8, after "oxide" (first occurrence), "carbon" and 'oxicle (second occurrence) delete the semi-colons and insert commas Signed and sealed this 11 th day of March 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCHALK Attesting Officer Commissioner of Patents 'ORM PC3-1050 (10-69) USCOMM-DC 60376-P69 U,SV GOVERNMENT PRINTING OFFICE 1969 035 633J 

2. A process in accordance with claim 1 wherein the basic solid adsorbent is selected from the group consisting of alumina, magnesium oxide, zinc oxide, titanium oxide, calcium oxide; activated carbon; barium oxide; bismuth trioxide and a ferric oxide.
 3. A process for preparing 4-(1-hydroxy-4-oxo-2,6,6-trimethyl-2-cyclohexene-1-yl)-3-butene-2-one which comprises bubbling air through a mixture consisting of 4-keto- Alpha -ionone, a basic solid adsorbent and an organic solvent for 4-keto- Alpha -ionone, said basic solid adsorbent being selected from the group consisting of metal oxides and activated carbon. 